Although immunization is a well-established process, there are differences in the response level elicited between different immunogens or antigens (used interchangeably herein). Of interest, membrane proteins form a class of antigens that produce a low response level, which in turn means that a large number of membrane proteins are required in order to generate or elicit an immune response to the desired level. Membrane proteins are notoriously difficult to synthesize and are insoluble in water without the presence of a detergent. This makes it expensive and difficult to obtain membrane proteins in sufficient quantity for the purpose of immunization.
Furthermore, membrane proteins require proper folding in order to function correctly. The immunogenicity of correctly folded membrane proteins are much better than solubilized membrane proteins, which are not folded in a physiologically relevant manner. Thus, even though adjuvants may be used to boost the immunogenicity of such solubilized membrane proteins, it is an inefficient method that does not provide too much of an advantage.
In addition, the common procedure to raise antibodies against membrane proteins often require a prior knowledge of their native structure within membranes in order to design suitable epitopes that can be used for the immunization. This immunization is usually performed independently using isolated peptides which could adopt conformations very differently from the one occurring in the full protein in its native membrane habitat. Hence, there is a high risk that the antibodies raised by the isolated peptides may not recognize the target protein in vivo after all.
Although transfected cells and lipid-based systems have been used to present membrane protein antigens to increase the chances of isolating antibodies that may efficient in vivo, these systems are often unstable, tedious and costly. Moreover, the current state of the art for such membrane protein antigens is to use inactive virus-like particles for immunization.
Therefore, there remains a need to provide for alternative methods that overcome, or at least alleviate, the above problems.